With its dense interacting populations of people, pigs, and poultry, China has been implicated as the source of the 1957 and 1968 pandemic influenza viruses and considered an epicenter for generating novel influenza virus strains. As industrialized farming has increased in China, the prevalence and variety of swine influenza viruses (SIVs) have increased. In this controlled, 5-yr project, we will collaborate with leading Chinese infectious disease researchers and employ a One Health approach (human, animal, and environment) to study SIV transmission in Confined Animal Feeding Operations (CAFOs) in mainland China. We will select CAFOs with a high prevalence of SIVs and prospectively follow the swine workers and their pigs, as well as examine the CAFO environment as a source for SIV persistence and transmission. In this collaboration, our aims are: 1) to identify and characterize enzootic and emergent SIVs, 2) to employ aerosol, fecal, environmental swabs, and water sampling to identify environmental areas with a high prevalence of SIVs, 3) to identify occupational risk factors for SIV infection, and 4) to identify serological and mucosal immunity biomarkers of protection against prevalent and emergent SIVs. This One Health approach to zoonotic influenza virus research is unique and made possible by our Chinese collaborators who have unique access to their swine production industry.